# NRAS

Source: https://onco.cc/targets/nras/  
OnCo record `nras` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

NRAS is one of the three RAS switch proteins that pass growth signals into the cell. When a mutation jams it on, as in a share of melanomas, the cell keeps dividing; today's drugs reach it indirectly through MEK or RAF, and pan-RAS inhibitors that bind the active form are in trials.

## Summary

NRAS (chromosome 1p13.2) encodes a small GTPase of the RAS-MAPK pathway that binds GDP and GTP, hydrolyses GTP and relays signals for proliferation and survival; its turnover is controlled by LZTR1-directed ubiquitination through a CUL3 ligase complex (UniProt P01111). In OnCo, NRAS appears as the mutation that defines the melanoma population for the MEK inhibitor tunlametinib (approved in China in 2024 for NRAS-mutant melanoma, a group with no targeted therapy elsewhere) and for the pan-RAF inhibitor naporafenib studied with trametinib; as a resistance marker, with KRAS, that excludes patients from cetuximab in colorectal cancer and that the Tempus xT CDx companion diagnostic reports; and as one of the three isoforms the pan-RAS(ON) inhibitor JYP0015 binds, covering mutations at codons 12, 13, 61, 117 and 146.

## Fields

- Kind: Target
- Last checked: 2026-09-22
- Also known as: N-ras; NRAS proto-oncogene, GTPase
- Tags: wave5-target
- Symbol: NRAS
- Class: oncogene
- Biology: RAS proteins share the GDP/GTP cycle and intrinsic GTPase activity; neurofibromin (NF1) stimulates that hydrolysis and so switches RAS off (UniProt P21359). Mutant NRAS stays GTP-bound, so the corpus drugs act below it (tunlametinib on MEK, naporafenib on RAF) or on the active state of all RAS isoforms (JYP0015). The lenzilumab record notes that chronic myelomonocytic leukaemia progenitors with NRAS, KRAS or CBL mutations proliferate in response to very low GM-CSF levels.
- Where found: Melanoma with NRAS mutation (tunlametinib, naporafenib); Colorectal cancer (RAS testing of KRAS and NRAS exons 2 to 4 before cetuximab; mutant tumours excluded); Chronic myelomonocytic leukaemia progenitors (lenzilumab rationale)

## Notes

- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.

## Sources

- HGNC HGNC:7989: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7989
- UniProt P01111: https://www.uniprot.org/uniprotkb/P01111/entry
- NCBI Gene 4893: https://www.ncbi.nlm.nih.gov/gene/4893

## Connected records

- drugs: [Cetuximab](https://onco.cc/drugs/cetuximab/), [JYP0015](https://onco.cc/drugs/jyp0015/), [Lenzilumab](https://onco.cc/drugs/lenzilumab/), [Naporafenib](https://onco.cc/drugs/naporafenib/), [Tempus xT CDx](https://onco.cc/drugs/tempus-xt-cdx/), [Tunlametinib](https://onco.cc/drugs/tunlametinib/)
- targets: [KRAS](https://onco.cc/targets/kras/), [MEK1/2](https://onco.cc/targets/mek/), [NF1 (neurofibromin)](https://onco.cc/targets/nf1/)
- cancers: [Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms](https://onco.cc/cancers/cmml/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Melanoma](https://onco.cc/cancers/melanoma/)
- technologies: [KRAS & RAS inhibitors](https://onco.cc/technologies/kras-inhibitors/)
- pathways: [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [Melanoma (KEGG map)](https://onco.cc/pathways/melanoma-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)

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JSON: https://onco.cc/api/v1/entities/nras.json